1. Field of the Invention
This invention relates to the field of tissue engineering, and in particular to animal-derived, bioremodelable, biopolymer scaffold materials used to repair animal tissue. The term “bioremodelable” or “bioremodelability” refers to a material that lends itself to the breakdown by cells that occupy it and use it as a template for creating a replacement made up mainly of newly synthesized components secreted by the cells.
Rebuilding the human body is a significant industry. Human tissue banks and synthetic polymers do not meet the need for repair or replacement of body parts. High on the list of alternative sources of material used to meet this need are animal tissues prepared in new ways that reduce their immunogenicity and maximize their usefulness and efficacy.
In the field of tissue engineering, the following three components are used alone or in combination to repair or create new tissue and organ substitutes, 1) scaffolds made of naturally-occurring polymers (e.g. collagens), man-made polymers, (e.g. PTFE, Dacron, PET or polyethylene) or sell-degrading, man-made polymers (e.g. PLA or PGA); 2) signaling molecules that give developmental instructions to cells; and 3) cells.
Man-made implant materials such as synthetic polymers, plastics, and surface-coated metals may have different degrees of immunogenicity and suffer from significant limitations that prohibit their broad applications. A major limitation is that cells cannot remodel them after implantation. They are highly susceptible to microbial infection, and some undergo calcification. Synthetic vascular conduits have a high incidence of occlusion after peripheral vascular bypass procedures.
2. Description of the Related Art
Several methods of preserving collagen-based matrices from animal tissues have been developed over the last decade (U.S. Pat. No. 4,801,299, issued Jan. 31, 1999; U.S. Pat. No. 5,336,616, issued Aug. 9, 1994; U.S. Pat. No. 5,756,678, issued; U.S. Pat. No. 5,916,265, issued Jun. 24, 1999; and U.S. Pat. No. 5,997,895, issued Dec. 7, 1999). All the methods include a chemical step that either kills or eliminates cells. Since tissues from post-natal animals or humans are the principal materials processed, a fixation step using glutaraldehyde or a similar agent may be used to mask antigenic determinants, eliminate the microbial burden and increase strength. However, aldehydic processing effectively destroys any biological activity, such as cell binding sites, associated with the original tissue and greatly reduces or eliminates the ability of cells to attach to it. It also eliminates binding sites for cell-synthesized products which attach to cells or to intermediates able to bind to cells and cell products that make up the extracellular matrix by cells.
Collagen-based devices that are animal-derived and fixed with glutaraldehyde or a similar agent can not be remodeled since they are highly resistant to metalloproteinase enzymes. The methods suggested in U.S. Pat. No. 4,801,299 and U.S. Pat. No. 5,916,265 include the use of glutaraldehyde or a similar agent for the fixation of tissue derived from a post-natal animal source; the resulting products can not be faithfully remodeled. Glutaraldehyde-treated devices are known to undergo gradual calcification. Heart valves made from fixed animal tissues can require replacement in 5-7 years or sooner due to calcification.
While detergents or sodium hydroxide may be used to process post-natal animal tissue (U.S. Pat. No. 4,801,299, U.S. Pat. No. 5,336,616, U.S. Pat. No. 5,756,678, U.S. Pat. No. 5,916,265, U.S. Pat. No. 5,997,895), they have not been used to process fetal or neo-natal animal tissue as used in U.S. application Ser. No. 09/871,518, referred to herein. For example, U.S. Pat. No. 5,997,895, filed Apr. 30, 1998, provides a certified collagen dura substitute derived from post-natal animal tissue that undergoes an alkaline/salt treatment involving sodium hydroxide and sodium sulfate (preferably in an aqueous solution of 5% sodium hydroxide and 20% sodium sulfate). A method for processing collagen containing materials which uses 1.0 N sodium hydroxide was disclosed in a journal article in 1989 by Diringer H. and Braig H. R. (Diringer H. and Braig H. R., 1989, Infectivity of unconventional viruses in dura mater. The Lancet, 439-440). This reference was cited in the FDA's Guide for 510(k) Review of Process Dura Mater (1990, 2).